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Chronic nicotine and synaptic transmission in brainstem respiratory neurons

脑干呼吸神经元的慢性尼古丁和突触传递

基本信息

批准号：
10401834
负责人：
Ralph Frank Fregosi
金额：
$ 37.4万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-10 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10401834
关键词：
ARHGEF5 gene Acetylcholine Action Potentials Acute Adolescence Age Animals Attenuated Birth Brain Brain Stem Breathing Carbon Dioxide Cells Chronic Data Deglutition Dendrites Development Devices Electronic cigarette Electrophysiology (science)Experimental Designs Exposure to Glutamates Glycine Goals Growth Homeostasis Human Milk Hypercapnia Immunohistochemistry In Vitro Injections Life Longevity Maintenance Mastication Measurement Membrane Membrane Potentials Mothers Motor Motor Neurons Muscle Nervous system structure Neuroanatomy Neurons Neurotransmitter Receptor Neurotransmitters Newborn Animals Nicotine Nicotinic Receptors Outcome Output Pattern Physicians Physiological Play Plethysmography Process Progress Reports Property Protocols documentation Pump Rattus Resistance Respiration Role Smokeless Structure Synapses Synaptic Transmission System Techniques Testing Time Tongue Weaning Work critical period drinking water electronic cigarette use experimental study gamma-Aminobutyric Acid gender difference hookah in utero in vivo neonatal period nervous system development nicotine exposure nicotine gum nicotine patch nicotine use patch clamp postnatal postsynaptic prenatal prenatal cigarette smoking prenatal exposure prenatal nicotine exposure presynaptic receptor expression relating to nervous system respiratory response sex social stressor suckling voltage

项目摘要

Despite a growing body of evidence showing that in utero nicotine exposure leads to aberrant development of brainstem neurons involved in the maintenance of key homeostatic functions such as breathing, the consumption of nicotine via smokeless nicotine delivery devices (e.g., e-cigarettes, water pipes, nicotine patches or gum) more than doubled between 2008-2012. A particular concern is raised by recent studies showing that 30% of pregnant smokers were advised to use nicotine patches or gum by their physician. To date, the majority of the data on nicotine exposure and development of brainstem neurons has focused on how in utero exposure alters the brains of very young neonatal animals. As a result, we do not know if the changes observed with in utero exposure resolve or persist with maturation, or worsen if exposure continues after birth. The specific objective of this application is to test the hypothesis that prenatal and/or postnatal exposure to nicotine alters the structure and function of brainstem neurons that control the muscles of the tongue (hypoglossal motor neurons, XIIMNs), using an in vitro approach, as well as the breathing-related control of the tongue muscles, using an in vivo approach. The tongue muscles participate in breathing, swallowing, suckling and mastication, and therefore are critical for organismal homeostasis. A key focus is whether abnormal development of the tongue muscle motor system is worsened if nicotine exposure continues after birth, or if the alterations persist or are attenuated if exposure ends at weaning. Animals (rats) will be studied at key developmental time points, including the early neonatal period (postnatal day 1 (P1) - P5); the putative critical period for development of brainstem neurons (P10 - P12); the end of adolescence when brain maturation is largely complete (P50 – P60); and after sexual and social maturity (4 – 6 months). Specific Aims: We will use neuroanatomy, immunohistochemistry, patch clamp electrophysiology and in vivo plethysmography and EMG recordings to examine how prenatal and/or postnatal nicotine exposure alters: 1) the dendrite branching pattern and the expression of inhibitory (GABA, glycine) and excitatory (glutamate) neurotransmitter receptors on XIIMNs; 2) development of important neuron membrane properties (resting potential, voltage threshold for spike initiation, etc.), the cell's response to excitatory and inhibitory neurotransmitters; 3) development of the breathing pattern and the function of tongue muscles during normal, quiet breathing and when breathing is increased in response to an acute nicotine challenge or by increasing inspired carbon dioxide. The proposed experiments will result in a comprehensive understanding of how in utero and life-long nicotine exposure alters development of brainstem motoneurons that are critical for survival.

尽管越来越多的证据表明胎儿在子宫内接触尼古丁会导致异常

项目成果

期刊论文数量（20）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Developmental nicotine exposure disrupts dendritic arborization patterns of hypoglossal motoneurons in the neonatal rat.

发育过程中的尼古丁暴露会破坏新生大鼠舌下运动神经元的树突状树枝化模式。

DOI：
10.1002/dneu.22379
发表时间：
2016
期刊：
Developmental neurobiology
影响因子：
3
作者：
Powell,GregoryL;Gaddy,Joshua;Xu,Fei;Fregosi,RalphF;Levine,RichardB
通讯作者：
Levine,RichardB

Current injection and receptor-mediated excitation produce similar maximal firing rates in hypoglossal motoneurons.

电流注射和受体介导的兴奋在舌下运动神经元中产生相似的最大放电率。

DOI：
10.1152/jn.00848.2015
发表时间：
2016
期刊：
Journal of neurophysiology
影响因子：
2.5
作者：
Wakefield,HilaryE;Fregosi,RalphF;Fuglevand,AndrewJ
通讯作者：
Fuglevand,AndrewJ

Developmental nicotine exposure alters AMPA neurotransmission in the hypoglossal motor nucleus and pre-Botzinger complex of neonatal rats.

DOI：
10.1523/jneurosci.3711-12.2013
发表时间：
2013-02-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Jaiswal SJ;Pilarski JQ;Harrison CM;Fregosi RF
通讯作者：
Fregosi RF

Influence of developmental nicotine exposure on glutamatergic neurotransmission in rhythmically active hypoglossal motoneurons.

发育期尼古丁暴露对节律性活跃舌下运动神经元谷氨酸能神经传递的影响。